The chemical name of Tadalafil is (6R, 12aR)-2, 3, 6, 7, 12, 12a-hexahydro-2-methyl 6-(3,4-methylenedioxyphenyl)-pyrazino[2′, 1′: 6,1]pyrido [3,4-b]indole-1, 4-dione and molecular formula is C22H19N3O4 and molecular weight is 389.41. The current pharmaceutical product contaning this drug is being sold by Icos-Lilly using tradename CIALIS, in the form of tablets.
Tadalafil of formula (I) is a tetra cyclic derivative, potent and selective inhibitor of cyclic guanosine 3,5-monophosphate-(cGMP)-specific phosphodiesterase type 5(PDE5) having utility in a variety of therapeutic area where such inhibition is thought to be beneficial. Therefore, it has utility in the treatment of various disorders, including stable, unstable and variant (Prinzmetal) angina, hypertension pulmonary hypertension, congestive heart failure, renal failure, arteiosclerosis, conditions of reduced blood vessel potency (post-PTCA) etc. Tadalafil is potent drug useful for treatment of erectile dysfunction.
U.S. Pat. No. 5,859,006 describes a process for the preparation of Tadalafil and its intermediate of formula (V) which involves reacting D-Tryptophan methyl ester of formula

With a piperonal of formula
in the presence of dichloromethane and trifluoroacetic acid which provides cis and trans isomers of compound of formula (V). The isomers are separated by chromatography. The cis isomer is then reacted with chloroacetyl chloride and methylamine to give Tadalafil of formula (I). The product of the reaction was purified by chromatography.
The above process has the certain disadvantages such as:    (a) The above process is time consuming and requiring 4–5 days at 0–5° C. for the completion of reaction.    (b) Overall yield obtained is low, with 37–42% cis isomer of (V), which is desired, and 27–47% trans isomer of (V) (undesired).    (c) It uses highly corrosive and toxic material Trifluoroacetic acid.    (d) All these processes require either fractional crystallization or column chromatography of the reaction mixture in order to separate the isomers before epimerization to form pure cis isomer of (V).    (e) The process requires 24–72 hours for epimerization in a volatile solvent like dichloromethane.
WO2004/011463 discloses process of preparation of Tadalafil via modified pictate-spengler reaction in which D-Tryptophan methyl ester hydrochloride and piperonal is condensed in anhydrous IPA to provide hydrochloride of compound of formula (V). The product further is reacted with chloroacetyl chloride and then with methyl amine to give Tadalafil of formula (I).
However this process requires anhydrous IPA specifically 0.1% or less water which is practically difficult thing.
WO2005/068464 discloses process of preparation in which D-Tryptophan methyl ester and piperonal is condensed in the presence of TFA, solvent and molecular sieves to give mixture of compound of formula (V) as cis and trans isomers which is treated with aq HCl to form hydrochloride salt of cis isomer which inturn is reacted with chloroacetyl chloride and then methylamine to give Tadalafil of formula (I).
However, in this process highly toxic and corrosive reagent trifloroacetic acid is used which should be avoided normally for regulatory compliance purpose.
In summary, the prior art relating to the process for the preparation of Tadalafil suffers with several drawbacks such as:    (a) The processes given in are time consuming and requiring 4–5days at 0–5° C. for the completion of reaction.    (b) Overall yield obtained is low, with 37–42% cis isomer of (V), which is desired, and 27–47% trans isomer of (V) (undesired).    (c) Highly corrosive and toxic material Trifluoroacetic acid is used in several patents.    (d) The processes require either fractional crystallization or column chromatography of the reaction mixture in order to separate the isomers before epimerization to form pure cis isomer of (V). The process also requires 24–72 hours for epimerization in a volatile solvent like dichloromethane.    (e) The process requires critical moisture check of the solvent like IPA in some patent.
The present inventors have directed their research work toward developing a process which solves above mentioned problems that is associated with the existing process.
Hence, there is need to overcome problems by developing an improved process, particularly processes that directly synthesize desired stereoisomer of the compound.